Anti‑Inflammatory and Hepatoprotective Roles of Oleic and Linoleic Acids in a Wistar Rat Model of Type 2 Diabetes

Anti‑Inflammatory and Hepatoprotective Roles of Oleic and Linoleic Acids in a Wistar Rat Model of Type 2 Diabetes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Anti‑Inflammatory and Hepatoprotective Roles of Oleic and Linoleic Acids in a Wistar Rat Model of Type 2 Diabetes Tony Augustine Ezike, Adams Olalekan Omoaghe, Adedamola Adediran Fafure, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8729494/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background The global rise in type 2 diabetes mellitus (T2DM) poses a major healthcare challenge, driven by chronic inflammation, oxidative stress, and hepatic dysfunction. Conventional therapies primarily target glycemic control but often fail to address tissue-level injury. Dietary fatty acids such as oleic acid (OA) and linoleic acid (LA) may offer adjunctive therapeutic benefits. Methods Eighty male Wistar rats (150–180g) were induced with T2DM using 10% fructose supplementation for six weeks followed by a single intraperitoneal injection of streptozotocin (35 mg/kg). Animals with fasting blood glucose > 250 mg/dL were randomized into eight groups (n = 10): normal control, non-diabetic + OA, non-diabetic + LA, diabetic control, diabetic + OA, diabetic + LA, diabetic + OA + LA, and diabetic + metformin. Treatments lasted six weeks. Plasma and pancreatic cytokines, oxidative stress markers, hepatic injury enzymes, and histological changes in liver and pancreas were assessed. Results Compared with diabetic controls, OA and LA significantly reduced pro-inflammatory cytokines (TNF-α, IL-6), increased anti-inflammatory IL-10, lowered malondialdehyde levels, and enhanced antioxidant enzyme activities (CAT, SOD) (p < 0.0001). Hepatic injury markers were normalized, and histological analysis revealed improved hepatic and pancreatic architecture. Combined OA + LA treatment produced synergistic benefits, including enhanced PDX-1 expression and greater histological restoration, though effects varied across parameters. Overall, OA and LA demonstrated efficacy comparable to metformin. Conclusion Oleic and linoleic acids exert anti-inflammatory, antioxidant, and hepatoprotective effects in a rat model of T2DM. Their combined administration showed synergistic benefits, underscoring the translational potential of dietary fatty acid modulation as an adjunctive strategy for managing T2DM-associated complications. Oleic acid Linoleic acid anti-inflammatory antioxidant hepatoprotective type 2 diabetes mellitus Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 13 Apr, 2026 Reviews received at journal 11 Mar, 2026 Reviews received at journal 28 Feb, 2026 Reviewers agreed at journal 25 Feb, 2026 Reviewers agreed at journal 22 Feb, 2026 Reviewers invited by journal 20 Feb, 2026 Editor assigned by journal 04 Feb, 2026 Submission checks completed at journal 04 Feb, 2026 First submitted to journal 29 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8729494","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":595052482,"identity":"02b6459e-0e96-49ae-974b-832549bd3b7f","order_by":0,"name":"Tony Augustine Ezike","email":"","orcid":"","institution":"Afe Babalola University","correspondingAuthor":false,"prefix":"","firstName":"Tony","middleName":"Augustine","lastName":"Ezike","suffix":""},{"id":595052483,"identity":"cd04674b-c4e7-4023-94f4-f33d0e731d0c","order_by":1,"name":"Adams Olalekan Omoaghe","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEElEQVRIiWNgGAWjYLACxgYGBj4G5gYQLQcSOPCAGC1sQBJEG4O1JJCiJbEBJIJPC7/Y4YMfv+6wkWNjP9j4cEbNnfT5YYcfAm2xk9NtwK5FcnZasrTsmTRjNp7EZsMNx57lbrydZgDUkmxsdgC7FoPbOQbSkm2HE9sYEtskH7Adzt04OwGk5UDiNtxajH9Ltv1PbON/2P7zwb/D6Yaz0z8Q0mIm+bHtQGKbRGIb48a2wwny0jn4bQH6Jc2asS3ZmE3iYbPkzL7DhhukcwoOJBjg9gu/dPLhmz/b7OT4+ZMPfuz5dlhefnb65g8fKuzkcGkBAWYeFKeCVRrgVg4CjD+QefIN+FWPglEwCkbByAMAXpZopoW5lbkAAAAASUVORK5CYII=","orcid":"","institution":"Afe Babalola University","correspondingAuthor":true,"prefix":"","firstName":"Adams","middleName":"Olalekan","lastName":"Omoaghe","suffix":""},{"id":595052484,"identity":"b8c7ea61-2d6f-4e92-9f1e-e96ea00acf95","order_by":2,"name":"Adedamola Adediran Fafure","email":"","orcid":"","institution":"Afe Babalola University","correspondingAuthor":false,"prefix":"","firstName":"Adedamola","middleName":"Adediran","lastName":"Fafure","suffix":""},{"id":595052485,"identity":"73fd27f6-b78b-455d-b65e-fef8fd063284","order_by":3,"name":"Kehinde Samuel Olaniyi","email":"","orcid":"","institution":"Afe Babalola University","correspondingAuthor":false,"prefix":"","firstName":"Kehinde","middleName":"Samuel","lastName":"Olaniyi","suffix":""}],"badges":[],"createdAt":"2026-01-29 09:23:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8729494/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8729494/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103506340,"identity":"6d714c01-ac24-46ee-8429-784d16e64976","added_by":"auto","created_at":"2026-02-26 13:35:24","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1188982,"visible":true,"origin":"","legend":"","description":"","filename":"MANUSCRIPT2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8729494/v1_covered_d0a40ed7-22c9-44eb-b14a-e72014a8158d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Anti‑Inflammatory and Hepatoprotective Roles of Oleic and Linoleic Acids in a Wistar Rat Model of Type 2 Diabetes","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"comparative-clinical-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Comparative Clinical Pathology](https://link.springer.com/journal/580)","snPcode":"580","submissionUrl":"https://submission.springernature.com/new-submission/580/3","title":"Comparative Clinical Pathology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Oleic acid, Linoleic acid, anti-inflammatory, antioxidant, hepatoprotective, type 2 diabetes mellitus","lastPublishedDoi":"10.21203/rs.3.rs-8729494/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8729494/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe global rise in type 2 diabetes mellitus (T2DM) poses a major healthcare challenge, driven by chronic inflammation, oxidative stress, and hepatic dysfunction. Conventional therapies primarily target glycemic control but often fail to address tissue-level injury. Dietary fatty acids such as oleic acid (OA) and linoleic acid (LA) may offer adjunctive therapeutic benefits.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eEighty male Wistar rats (150\u0026ndash;180g) were induced with T2DM using 10% fructose supplementation for six weeks followed by a single intraperitoneal injection of streptozotocin (35 mg/kg). Animals with fasting blood glucose\u0026thinsp;\u0026gt;\u0026thinsp;250 mg/dL were randomized into eight groups (n\u0026thinsp;=\u0026thinsp;10): normal control, non-diabetic\u0026thinsp;+\u0026thinsp;OA, non-diabetic\u0026thinsp;+\u0026thinsp;LA, diabetic control, diabetic\u0026thinsp;+\u0026thinsp;OA, diabetic\u0026thinsp;+\u0026thinsp;LA, diabetic\u0026thinsp;+\u0026thinsp;OA\u0026thinsp;+\u0026thinsp;LA, and diabetic\u0026thinsp;+\u0026thinsp;metformin. Treatments lasted six weeks. Plasma and pancreatic cytokines, oxidative stress markers, hepatic injury enzymes, and histological changes in liver and pancreas were assessed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eCompared with diabetic controls, OA and LA significantly reduced pro-inflammatory cytokines (TNF-α, IL-6), increased anti-inflammatory IL-10, lowered malondialdehyde levels, and enhanced antioxidant enzyme activities (CAT, SOD) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Hepatic injury markers were normalized, and histological analysis revealed improved hepatic and pancreatic architecture. Combined OA\u0026thinsp;+\u0026thinsp;LA treatment produced synergistic benefits, including enhanced PDX-1 expression and greater histological restoration, though effects varied across parameters. Overall, OA and LA demonstrated efficacy comparable to metformin.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOleic and linoleic acids exert anti-inflammatory, antioxidant, and hepatoprotective effects in a rat model of T2DM. Their combined administration showed synergistic benefits, underscoring the translational potential of dietary fatty acid modulation as an adjunctive strategy for managing T2DM-associated complications.\u003c/p\u003e","manuscriptTitle":"Anti‑Inflammatory and Hepatoprotective Roles of Oleic and Linoleic Acids in a Wistar Rat Model of Type 2 Diabetes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-24 17:25:34","doi":"10.21203/rs.3.rs-8729494/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-13T08:13:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-11T23:59:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-28T17:43:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"285320924550568998958224198865584078781","date":"2026-02-25T12:01:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"247725635694518438132767743180932777140","date":"2026-02-22T06:30:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-20T06:18:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-04T22:02:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-04T21:59:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"Comparative Clinical Pathology","date":"2026-01-29T08:40:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"comparative-clinical-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Comparative Clinical Pathology](https://link.springer.com/journal/580)","snPcode":"580","submissionUrl":"https://submission.springernature.com/new-submission/580/3","title":"Comparative Clinical Pathology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"1583a4f3-ab9b-4f96-ab75-bfe73c7a4f68","owner":[],"postedDate":"February 24th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-27T09:23:24+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-24 17:25:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8729494","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8729494","identity":"rs-8729494","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}